Clinical trial of H5N1 flu vaccine to begin

Editor's note: This story was revised Mar 24 to include additional information obtained in an interview with Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases.

Mar 23, 2005 (CIDRAP News) – Three universities have begun recruiting volunteers for the first US clinical trial of a vaccine against H5N1 avian influenza, a key piece of the government's efforts to stave off a potential flu pandemic.

Researchers plan to recruit 450 adults to test the safety and immunogenicity of a vaccine made from an H5N1 virus isolated in Asia in 2004, the National Institute of Allergy and Infectious Diseases (NIAID) announced today.

"The initiation of this vaccine trial marks a key advance in our efforts to prepare to respond to an avian flu pandemic," said NIAID Director Anthony S. Fauci, MD, in a news release.

The phase 1 trial will take place at the University of California at Los Angeles, the University of Maryland in Baltimore, and the University of Rochester in New York. The principal investigators are Joel Ward, MD, at UCLA; James Campbell, MD, at Maryland; and John Treanor, MD, at Rochester.

The vaccine is made by Sanofi Pasteur (formerly Aventis Pasteur), Swiftwater, Pa. The NIAID awarded the company a contract to produce 8,000 to 10,000 doses of the vaccine in May 2004.

The trial "will test the vaccine's safety and ability to generate an immune response in 450 healthy adults aged 18 to 64," the NIAID said. "If the vaccine is shown to be safe in adults, there are plans to test it in other populations, such as the elderly and children."

Fauci told CIDRAP News in a phone interview that the vaccine will be tested in elderly people second and then in children. Each of these age-group trials will take "a couple of months," and completing all of them is likely to take close to a year, he said.

Last fall Fauci had predicted that clinical trials of the vaccine would probably begin in January. The Sanofi vaccine trial was delayed by technical issues such as indemnification and liability, but those "have now been totally cleared," he said in the interview. "Now people are being enrolled in the trial and will receive the vaccine literally within a couple of days."

A University of Rochester news release said the clinical trial will be carried out in two stages. In the first stage, a total of 113 people at all three sites, including 40 in Rochester, will receive two injections 4 weeks apart and will be monitored for side effects. After safety data from the first stage have been reviewed, the remaining 337 people will receive one of four different doses of the vaccine and will be monitored. The whole trial will take 7 months, the statement said.

Chiron Corp. also won an NIAID contract in May 2004 to produce pilot lots of an H5N1 vaccine for clinical trials. Fauci said a clinical trial of that vaccine will be getting under way soon.

The Chiron vaccine is being made in Liverpool, England, but not in the same plant where contamination problems last fall led to the loss of about half of the expected US supply of flu vaccine for the 2004-05 season, Fauci explained. He said the company asked British authorities to reinspect the H5N1 vaccine plant to make sure it didn't have any contamination, and that process has delayed the trial of the vaccine.

"This plant didn't have documented contamination, but they just wanted to be sure it didn't have an issue, so they asked for an inspection, and it has passed the inspection but it has set them back a couple months," Fauci said.

Besides making H5N1 vaccine for clinical trials, Sanofi Aventis has a federal contract to produce 2 million doses of the vaccine for possible use by public health and laboratory workers in the event of a pandemic. The contract is also intended to help the company prepare for mass production in case a pandemic erupts, the NIAID has said.

Fauci said Sanofi is "well into" making the 2 million doses. "The critical issue with the 2 million doses is they're made under conditions where they are easily able to be scaled up" if the need arises, he said. "So if you make it in bulk you're halfway there."

Unofficially, 71 human cases of H5N1 infection have occurred in Asia since January 2004, and 47 of the patients died. Nearly all of those cases have been attributed to exposure to sick poultry. The virus has shown little ability to spread from person to person, but if it acquired that ability, experts fear, it could trigger a pandemic.